Human papillomaviruses are one of the principal infectious agents known to cause cancers in humans; it is estimated that approximately 5% of cancers worldwide are attributable to HPV infection. While it is well established that HPV is a necessary cause of cervical cancer, world experts agree that for HPV16, the most carcinogenic of the HPV genotypes, data show a causal role in cancers outside the cervix, including the vulva, vagina, penis, and anus, and some head and neck tumors in the oropharynx. Other cancers hypothesized to be related to HPV infection, but for which a causal association has yet to be shown, include cancers of the oral cavity, larynx, conjunctiva, and, for cutaneous HPV types, skin. To that end, considerable research within the IIB focuses on the role of HPV infection in cancer at extra-cervical sites. We have many on-going studies whose aims are to: 1) evaluate the natural history of HPV infections at non-cervical sites 2) determine the prevalence and biologic activity of HPV infection in tumors from these sites 3) assess the prospective association between HPV infection and risk of extra-cervical prevalent, incident, and recurrent cancers 4) evaluate the efficacy of the HPV16/18 prophylactic vaccine against extra-cervical infections